Calcium-deficient silicate-substituted calcium phosphate apatite compositions and methods

Abstract

A calcium-deficient silicate-substituted calcium phosphate apatite composition comprises an apatite phase having a Ca/P molar ratio of from greater than 2.15 to 2.30, and a Ca/(P+Si) molar ratio of from 1.45 to 1.55. A method of producing a calcium-deficient silicate-substituted calcium phosphate apatite composition comprises contacting a silicate-substituted calcium phosphate apatite starting material with an acidic solution to produce the calcium-deficient silicate-substituted calcium phosphate apatite composition. The starting material comprises an apatite phase and up to 15 wt % total of a phase or phases other than the apatite phase, and has a Ca/P molar ratio of from 2.3 to 2.6, and a Ca/(P+Si) molar ratio of from 1.56 to 1.66, and the calcium-deficient silicate-substituted calcium phosphate apatite composition comprises an apatite phase having a Ca/P molar ratio lower than the Ca/P ratio of the starting material apatite phase.

1 . A calcium-deficient silicate-substituted calcium phosphate apatite composition comprising an apatite phase having a Ca/P molar ratio of from greater than 2.15 to 2.30, and a Ca/(P+Si) molar ratio of from 1.45 to 1.55. 
     
     
         2 . The composition according to  claim 1 , wherein the apatite phase has a Ca/P molar ratio of from greater than 2.15 to 2.28, from 2.20 to 2.30, or from 2.20 to 2.28. 
     
     
         3 . The composition according to  claim 1 , wherein the apatite phase has a Ca/(P+Si) molar ratio of from 1.45 to 1.54, or from 1.45 to 1.52. 
     
     
         4 . The composition according to  claim 1 , having a silicon content of 4 to 6 wt %. 
     
     
         5 . The composition according to  claim 1 , densified by sintering at a temperature of from 1100 to 1300° C. 
     
     
         6 . The composition according to  claim 1 , comprising up to 5 wt % total of a phase or phases other than the apatite phase, and the composition has Ca/P molar ratio of from greater than 2.15 to 2.35, and a Ca/(P+Si) molar ratio of from 1.45 to 1.60. 
     
     
         7 . The composition according to  claim 1 , wherein the composition consists or consists essentially of the apatite phase. 
     
     
         8 . A method of producing a calcium-deficient silicate-substituted calcium phosphate apatite composition, comprising contacting a silicate-substituted calcium phosphate apatite starting material with an acidic solution to produce the calcium-deficient silicate-substituted calcium phosphate apatite composition,
 wherein the starting material comprises an apatite phase and has a Ca/P molar ratio of from 2.3 to 2.6, and a Ca/(P+Si) molar ratio of from 1.56 to 1.66, and   wherein the calcium-deficient silicate-substituted calcium phosphate apatite composition comprises an apatite phase having a Ca/P molar ratio which is lower than the Ca/P ratio of the starting material apatite phase before contact with the acidic solution.   
     
     
         9 . A method according to  claim 8 , wherein the starting material comprises a silicon atom content of from 4 to 6 wt %. 
     
     
         10 . A method according to  claim 8 , wherein the starting material comprises up to 15 wt % total of a phase or phases other than the apatite phase. 
     
     
         11 . A method according to  claim 8 , wherein the starting material comprises a material according to formula (I):
   Ca 10-δ (PO 4 ) 6-x (SiO 4 ) x (OH) 2-y   (I)
   wherein 1.1≤x≤2.0, 1.0≤y 2.0, and δ represents a Ca deficiency.   
     
     
         12 . A method according to  claim 8 , wherein the starting material is a powder with a specific surface area of from 10 to 90 m 2 /g. 
     
     
         13 . A method according to  claim 8 , wherein the starting material is a powder with a D v 50 less than 100 μm, or comprises granules having an average particle diameter D v 50 greater than 100 μm. 
     
     
         14 . A method according to  claim 8 , wherein the acidic solution is an aqueous acidic solution. 
     
     
         15 . A method according to  claim 8 , wherein the acidic solution comprises an acid component and a liquid vehicle, wherein the acid component is an acid having a pKa of greater than −1.73. 
     
     
         16 . A method according to  claim 8 , wherein the acidic solution comprises or consists of an aqueous ammonium chloride solution. 
     
     
         17 . A method according to  claim 16 , wherein the aqueous ammonium chloride solution has an ammonium chloride concentration of from 0.01% w/v to 15% w/v. 
     
     
         18 . A method according to  claim 8 , comprising mixing the acidic solution and the starting material in a weight ratio of at least 5:1. 
     
     
         19 . A method according to  claim 8 , comprising incubating the mixture of the starting material and the acidic solution for a predetermined period of time. 
     
     
         20 . A method according to  claim 19 , wherein incubating the mixture comprises heating the incubation mixture to a temperature T 1  and allowing the incubation mixture to remain at temperature T 1  for a time t 1 , wherein T 1  is at least 30° C. and t 1  is at least 10 mins. 
     
     
         21 . A method according to  claim 8 , comprising separating the calcium-deficient silicate-substituted calcium phosphate apatite composition from the acidic solution. 
     
     
         22 . A method according to  claim 8 , further comprising one or more steps of sintering the calcium-deficient silicate-substituted calcium phosphate apatite composition at a temperature of at least 100° C. 
     
     
         23 . A method according to  claim 8 , wherein the calcium-deficient silicate-substituted calcium phosphate apatite composition comprises a Ca/(P+Si) molar ratio which is lower than the Ca/(P+Si) ratio of the starting material before contact with the acidic solution. 
     
     
         24 . A method according to  claim 8 , wherein the calcium-deficient silicate-substituted calcium phosphate apatite composition comprises a Ca/P molar ratio of from greater than 2.15 to 2.35 and a Ca/(P+Si) molar ratio of from 1.45 to 1.60. 
     
     
         25 . A method according to  claim 8 , wherein the calcium-deficient silicate-substituted calcium phosphate apatite composition comprises a silicon atom content of from 4 to 6 wt %. 
     
     
         26 . A method according to  claim 8 , wherein the calcium-deficient silicate-substituted calcium phosphate apatite composition comprises an apatite phase having a Ca/P molar ratio of from greater than 2.15 to 2.30, and a Ca/(P+Si) molar ratio of from 1.45 to 1.55. 
     
     
         27 . A calcium-deficient silicate-substituted calcium phosphate apatite composition obtained or obtainable by a method according to  claim 8 . 
     
     
         28 .- 29 . (canceled) 
     
     
         30 . A medical device comprising a coating which includes a calcium-deficient silicate-substituted calcium phosphate apatite composition according to  claim 1 . 
     
     
         31 . A macroporous ceramic bone graft substitute comprising a calcium-deficient silicate-substituted calcium phosphate apatite composition according to  claim 1 . 
     
     
         32 . (canceled) 
     
     
         33 . A method of treating a disease or disorder requiring the replacement of bone tissue, comprising replacing bone tissue with a calcium-deficient silicate-substituted calcium phosphate apatite composition according to  claim 1 . 
     
     
         34 . A method according to  claim 8 , wherein the acidic solution improves the thermal stability of the calcium-deficient silicate-substituted calcium phosphate apatite phase.